HIF-1 transcription activity: HIF1A driven response in normoxia and in hypoxia

Flora Cimmino1,2, Marianna Avitabile3,4, Vito Alessandro Lasorsa3,4

  • 1Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy. cimminof@ceinge.unina.it.

BMC Medical Genetics
|February 28, 2019
PubMed
Abstract

Insights

Hypoxia-Inducible-Factor 1A (HIF1A) drives tumor resistance. Identifying HIF1A targets and signatures under varying oxygen levels can improve prognosis and therapy for solid tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Hypoxia-Inducible-Factor 1A (HIF1A) expression contributes to therapeutic resistance in solid tumors.
  • Current therapies targeting hypoxia signaling show limited clinical efficacy due to fluctuating oxygen levels in tumors.
  • Identifying stable HIF1A targets and hypoxia signatures could enhance prognostic stratification and treatment outcomes for high-risk solid tumors.

Purpose of the Study:

  • To investigate the combined effects of RNA expression and DNA methylation on HIF1A activity in neuroblastoma cells under normoxia and hypoxia.
  • To identify molecular mechanisms underlying HIF1A-driven gene expression changes in response to varying oxygen conditions.
  • To discover novel HIF1A-dependent and independent signatures for patient risk stratification in solid tumors.

Main Methods:

  • Combined analysis of RNA expression and DNA methylation data.
  • Culturing neuroblastoma cells under normoxia and hypoxia with HIF1A silenced or unsilenced.
  • Pathway analysis to identify key biological processes regulated by HIF1A.

Main Results:

  • HIF1A activity influences metabolic processes in normoxia and neuronal differentiation in hypoxia.
  • Epigenetic modifications, specifically DNA methylation, regulate HIF1A's transcriptional response in hypoxia.
  • Identified HIF1A-dependent and independent signatures that stratify patients into different risk categories based on oxygen levels.

Conclusions:

  • Understanding how low oxygen levels alter gene signatures is crucial for developing effective hypoxia-targeting strategies in solid tumors.
  • The identified HIF1A-driven mechanisms and patient signatures offer new directions for improving therapeutic success in high-risk cancers.

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